Clinical Review

Role of nutrition in preventing cancer

Richard Béliveau PhD  Denis Gingras PhD

ABSTRACT

OBJECTIVE  To summarize the evidence linking dietary habits to the incidence of several types of cancer with
special emphasis on the chemoprotective properties of foods that originate from plants.

QUALITY OF EVIDENCE  A large body of epidemiologic, animal, and laboratory literature indicates that as many
as 30% of all cancer cases are linked to poor dietary habits. The proportion reaches 70% for cancers of the
gastrointestinal tract.

MAIN MESSAGE  Studies have consistently linked abundant consumption of plant-based food to a substantial
reduction in risk of developing various cancers. Laboratory studies show that this chemopreventive effect is
related to the high levels of numerous phytochemicals in this food. These phytochemicals interfere with several
cellular processes involved in the progression of cancer and also with inflammatory processes that foster
development of cancer.

CONCLUSION  Dietary factors play an important role in the high incidence of several types of cancer in Canada.
Modification of dietary habits to include daily intake of plant-based food containing anticancer and anti-
inflammatory phytochemicals thus represents a promising approach to preventing the development of cancer.

Résumé

OBJECTIF  Faire le point sur les données qui indiquent que l’incidence de plusieurs types de cancers est reliée
aux habitudes alimentaires, en insistant particulièrement sur les propriétés chimioprotectrices de certains
aliments d’origine végétale.

QUALITÉ DES PREUVES  Les résultats d’un grand nombre d’études épidémiologiques et d’expériences chez
l’animal ou en laboratoire indiquent que jusqu’à 30% de tous les cas de cancer sont liés à de mauvaises
habitudes alimentaires. Pour les cancers du tube digestif, cette proportion atteint 70%.

PRINCIPAL MESSAGE  Les études ont régulièrement montré que la consommation d’une bonne quantité
d’aliments d’origine végétale est associée à un risque considérablement moindre de développer certains
types de cancers. Les études en laboratoire révèlent que cet effet chimioprotecteur est dû aux niveaux élevés
de plusieurs phytochimiques contenus dans ces aliments. Ces phytochimiques interfèrent avec plusieurs des
processus cellulaires nécessaires à la progression du cancer et ralentissent les processus inflammatoires qui
favorisent son développement.

CONCLUSION  Divers facteurs alimentaires jouent un rôle important dans l’incidence élevée de plusieurs
types de cancer au Canada. Un changement dans les habitudes alimentaires favorisant un apport quotidien
d’aliments d’origine végétale riches en phytochimiques anticancéreux et anti-inflammatoires représente donc
une stratégie prometteuse pour prévenir le cancer.

This article has been peer reviewed.

Cet article a fait l’objet d’une révision par des pairs.
Can Fam Physician 2007;53:1905-1911

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Clinical Review  Role of nutrition in preventing cancer

I
n their landmark study, Doll and Peto showed that relationship is strengthened by a large body of evidence
75% to 80% of all cancers diagnosed in the United derived from animal and laboratory studies.
States in 1970 might have been prevented by altering Many epidemiologic studies have consistently linked
lifestyle factors, such as smoking and diet.1 Subsequently, abundant consumption of foods of plant origin, such
their conclusions were confirmed by a large number of as fruit, vegetables, whole grains, legumes, nuts, seeds,
studies. Researchers currently estimate that diet could and tea, with decreased risk of developing various of
account for approximately 30% of cancer deaths, similar cancers.2,5 When results of studies on all types of can-
to the number accounted for by smoking.2 cer are taken together, as many as 80% show a sub-
The close relationship between diet and cancer is sug- stantial decrease in risk with higher intake of at least 1
gested by the large variation in rates of specific cancers vegetable or fruit category examined2 (Table 12). This
in different countries and by the spectacular changes is particularly true for cancers of the upper gastroin-
observed in the incidence of cancer in migrating popu- testinal tract (Table 22); for example, studies indicate
lations.1-3 For example, studies have shown that Asians that as many as 75% of colorectal cancers, the second
have a 25-fold lower incidence of prostate cancer and leading cause of death due to cancer in Canada, could
a 10-fold lower incidence of breast cancer than inhab- be prevented by increasing the amount of plant-based
itants of Western countries do, but that rates of these food in the diet.6
cancers dramatically increase following migration to the These observations suggest that food of vegetable
West.2 The importance of lifestyle factors in the devel- origin is an essential source of molecules with chemo-
opment of cancer was also shown in studies of mono- preventive properties. This hypothesis is strengthened
zygotic twins (who share all genes). Inherited genetic by many experimental data obtained from studies using
factors were shown to be responsible for only about cellular and animal models in which molecules isolated
15% of all cancer cases.4 These observations indicate
that most cancers are not of hereditary origin and that Table 1. Summary of results of case-control and
lifestyle factors, such as dietary habits, have a profound cohort studies of all types of cancer showing an
influence on their development. inverse association between consumption of various
categories of fruit and vegetables and risk of cancer:
Quality of evidence Overall level of evidence is I.
Relevant papers were identified by searching PubMed % OF TOTAL
FRUIT OR NO. OF STUDIES STUDIES
from January 1980 to December 2006 using the key
VEGETABLE SHOWING TOTAL NUMBER SHOWING
words cancer, diet, prevention, angiogenesis, inflammation, CATEGORIES DECREASED RISK OF STUDIES DECREASED RISK
and phytochemicals. Articles on the chemopreventive All vegetables 59 74 80
potential of specific foods or food groups were sought
All fruit 36 56 64
using the key words for these groups (eg, cruciferous,
allium, soy, citrus, tomato, turmeric, berries, and green
Raw 40 46 87
vegetables
tea) or the key words for the anticancer molecules found
in these foods (eg, isothiocyanates, sulforaphane, sulfides, Cruciferous 38 55 69
vegetables
resveratrol, curcumin, and epigallocatechin-3-gallate).
Evidence of the chemopreventive effects of various Allium 27 35 77
components of food comes from several hundred case- vegetables
control and prospective epidemiologic studies, and this Green 68 88 77
vegetables
Levels of evidence Tomatoes 36 51 71
Citrus fruit 27 41 66
Level I: At least one properly conducted randomized Adapted from American Institute for Cancer Research.2
controlled trial, systematic review, or meta-analysis
Level II: Other comparison trials, non-randomized, Table 2. Levels of evidence for decreased risk of
cohort, case-control, or epidemiologic studies, and various types of cancer with consumption of fruit and
preferably more than one study vegetables
Level III: Expert opinion or consensus statements TYPE OF CANCER LEVEL OF EVIDENCE

Stomach, esophagus, mouth and I

pharynx, colon, rectum, lung
Drs Béliveau and Gingras are researchers in the
Larynx, pancreas, breast, bladder II
Laboratoire de Médecine Moléculaire Ste-Justine at the
University of Quebec at Montreal and in the Service
Ovary, endometrium, cervix, thyroid, III
prostate, kidney, liver
d’hématologie-oncologie in the Centre de Cancérologie
Adapted from American Institute for Cancer Research.2
Charles-Bruneau at the Hôpital Ste-Justine in Montreal.

1906  Canadian Family Physician • Le Médecin de famille canadien  Vol 53:  november • novembre 2007
 Role of nutrition in preventing cancer  Clinical Review
from various food sources were found to interfere with implies that precancerous cells have overwhelmed these
development of several cancers.7,8 defences and acquired the ability to grow and invade
the host tissues.
Interfering with the
development of precancerous tumours Anticancer properties of plant-based food:
Carcinogenesis is generally a slow process during which the importance of phytochemicals
precancerous cells must accumulate several mutations There is now considerable evidence that the chemo-
in the genes involved in growth control, resistance to preventive properties of plant-based food are related
apoptosis, and induction of angiogenesis in order to to their ability to block the progression of latent micro-
grow and invade the host tissues9 (Figure 110). This pro- tumours. These properties arise from the high content
cess, which might take place over several years (even of phytochemicals, molecules that target several key
several decades), offers a large therapeutic window for events in the development of cancer. Intensive research
blocking the development of cancer. The low genetic conducted over the last few years has shown that phy-
diversity of precancerous cells and the absence of an tochemicals derived from the diet interfere with tumour
appropriate blood supply render the cells much more progression by acting directly on tumour cells as well as
vulnerable to anticancer molecules than mature tumour by modifying the tumour’s microenvironment (stroma)
cells would be. and creating physiologic conditions that are hostile to
Preventing cancer by blocking development of these tumour growth.
precancerous cells is extremely important because
even healthy people have a certain number of latent Direct inhibitory actions on tumour cells.
tumours in their tissues. Studies of people who died Reduction of damage to DNA:  Free radicals,
from causes unrelated to cancer have shown that 30% environmental or diet-associated chemicals, and some
to 50% of women aged 40 to 50 years had premalig-
Table 3. Proportion of tumours detected at autopsy and
nant microscopic breast tumours, and 40% of similarly
clinically: Tumours had formed spontaneously.
aged men had precancerous cells in the prostate.11 Even
% OF PATIENTS with % OF PATIENTS with
more striking, virtually every person (98%) had small TUMOURS DETECTED AT TUMOURS DETECTED
latent tumours in the thyroid, although these tumours ORGAN AUTOPSY CLINICALLY
are only very rarely observed in the clinic (Table 311). Breast (40- to 50- 33 1
It thus seems that the spontaneous formation of small year-old women)
tumours happens frequently over a lifetime, but that Prostate (40- to 40 2
in most cases the growth of these small tumours is 50-year-old men)
tightly controlled by our natural defence mechanisms,
Thyroid 98 0.1
and they remain in a microscopic and harmless state.12
Adapted from Black and Welch. 11
The appearance of clinically detectable cancer thus

Figure 1. Steps in carcinogenesis: For many years, or even decades, cancerous cells remain very vulnerable;
only a few will succeed in reaching the malignant stage. This vulnerability makes it possible to intervene and
interfere at several stages of tumour development and thus prevent onset of disease.

Adapted from Béliveau and Gingras.10

Vol 53:  november • novembre 2007  Canadian Family Physician • Le Médecin de famille canadien  1907
Clinical Review  Role of nutrition in preventing cancer
metabolites all have the capacity to severely damage cell
DNA, which might ultimately lead to cancer.13 Several
chemopreventive phytochemicals elicit their anticancer
effects by modulating the enzymatic systems responsi-
ble for neutralizing these carcinogens, either by reducing
their carcinogenic potential or by increasing their excre-
tion.14-16 For example, isothiocyanates, compounds found
in abundance in cruciferous vegetables, inhibit tumouri-
genesis by reducing genetic damage induced by a wide
variety of chemical carcinogens. 17,18 Phytochemicals,
which modulate the host’s defence mechanism against
DNA-damaging molecules, are also found in several
other types of fruit and vegetables, including members
of the genus Allium (such as garlic)19 and citrus fruit.20
The ability of these molecules to reduce the oncogenic
potential of carcinogens thus makes them an efficient
first-line defence against cancer.16-19
Cytotoxicity against tumour cells: Several phytochem-
icals also inhibit tumour growth by directly inducing
cancer cell death by apoptosis. For example, phenethyl
isothiocyanate from cruciferous vegetables, curcumin
from turmeric, and resveratrol from grapes have all been
shown to possess strong pro-apoptotic activity against
cells isolated from a variety of tumours.21-23 This activity
correlates with inhibition of tumour growth in animals.
Recent work has shown that some phytochemicals also
sensitize tumour cells to apoptotic cues derived from
natural pro-apoptotic stimuli, such as tumour necrosis
factor–related apoptosis-inducing ligand.24,25 Overall, the
cytotoxic properties of diet-derived phytochemicals con-
tribute to the chemopreventive effects associated with
intake of plant-derived foods and could play an essen-
tial role in preventing growth of cells that have already
acquired an initiated phenotype (precancerous cells).
Effects on tumour microenvironment.
Antiangiogenic properties: Angiogenesis is the pro-
cess by which tumour cells stimulate formation of new
blood vessel networks that sustain the development of
cancer by providing oxygen and nutrients to tumour
cells.26 Work from our laboratory has shown that several
phytochemicals possess strong antiangiogenic activ-
ity and that this effect likely plays an important role
in their chemopreventive properties.27,28 For example,
epigallocatechin-3-gallate (EGCG), an abundant poly-
phenol found in green tea, potently inhibits vascular
endothelial growth factor receptor-2, a key receptor
involved in tumour angiogenesis.29 The inhibitory effect
occurs with low concentrations of EGCG (concentrations
achievable through diet), suggesting that this antiangio-
genic effect is relevant in vivo.28 Accordingly, oral infu-
sion of a polyphenolic fraction isolated from green tea at
a human achievable dose (equivalent to 6 cups of green
tea per day) strongly inhibits development of prostate
cancer and increases the survival of transgenic mice
that spontaneously develop this cancer.30 Interestingly,
1908  Canadian Family Physician • Le Médecin de famille canadien  Vol 53:  november • novembre 2007
moderate consumption of green tea by humans was
also recently associated with clear clinical benefits for
some patients with chronic lymphocytic leukemia.31
In a similar manner, ellagic acid,32 a phenolic acid
found in high quantities in some fruit, such as rasp-
berries and strawberries, and delphinidin,33 an antho-
cyanidin abundant in blueberries, also block vascular
endothelial growth factor receptor-2 activity and also
strongly inhibit the activity of another receptor found in
perivascular cells, platelet-derived growth factor recep-
tor. 32,33 This combined inhibitory effect of 2 receptor
tyrosine kinases that are both essential for angiogenesis
leads to inhibition of this process in both in vitro and
in vivo assays29,33 in a manner similar to the synergistic
anticancer effects observed with pharmacologic inhibi-
tion of these receptors.34 There is growing evidence that
the antiangiogenic effects of these phytochemicals play
a crucial role in their chemopreventive activity by pre-
venting latent tumours from acquiring the blood vessel
network necessary to sustain their growth and permit
them to invade host tissues.
Anti-inflammatory effects: It is becoming increas-
ingly clear that inflammatory stimuli participate in the
progression of several cancers, including those of the
colorectum, breast, and lung.35 The close relationship
between inflammation and cancer is suggested by the
identification of a number of inflammatory conditions
that predispose patients to cancer (Table 436) as well as
by the chemopreventive effects that anti-inflammatory
cyclooxygenase-2 (COX-2) inhibitors, such as celecoxib,
have on risk of colorectal cancer.37 Although the severe
cardiovascular side effects associated with these drugs
preclude their use as prophylactic agents,38 these effects
nevertheless indicate that reducing inflammation repre-
sents a promising approach to preventing cancer.
Table 4. Some inflammatory conditions that predispose
patients to cancer
INFLAMMATORY STIMULUS MALIGNANCY
Inflammatory bowel disease Colorectal cancer
Helicobacter pylori-induced Gastric cancer
gastritis
Prostatitis Prostate cancer
Salpingitis, endometriosis Ovarian cancer
Barrett syndrome Esophageal cancer
Asbestos inhalation Bronchial carcinoma,
mesothelioma
Adapted from Balkwill et al.36
There is now considerable evidence that Western
diets rich in refined starches, sugar, and saturated and
trans fatty acids and poor in fruit, vegetables, fibre, ω-3
fatty acids, and whole grains promote inflammation.39
Inflammatory and immune cells from those consum-
ing typical Western diets contain a high proportion
 Role of nutrition in preventing cancer  Clinical Review
of the pro-inflammatory ω-6 polyunsaturated fatty
acid (PUFA) arachidonic acid and a low proportion of
Figure 2. Including foods with chemopreventive
anti-inflammatory ω-3 PUFAs eicosapentenoic acid and
properties in a daily diet
docosahexenoic acid.40 As arachidonic acid is the pre-
cursor of 2-series prostaglandins and 4-series leukotri-
enes, which are highly active mediators of inflammation,
a high dietary ω-6–to–ω-3 ratio results in generation of
a pro-inflammatory state that could sustain the onset of
several diseases, including cardiovascular disease, dia-
betes, and certain types of cancer.39,41
In addition to the important role of dietary PUFAs,
there is also growing evidence that several phytochemi-
cals from dietary sources reduce inflammatory processes,
and that this anti-inflammatory effect contributes to
their anticancer properties.42 For example, curcumin (the
yellow pigment of turmeric), the green tea polyphenol
EGCG, and resveratrol from grapes have all been shown
to markedly reduce the expression of COX-2, an effect
related to blockading the activity of the nuclear factor-
κB transcription factor.7,42,43 This effect is likely to occur
in humans, as reflected by the decrease in serum levels
of the inflammatory prostaglandin PGE2 following oral
administration of curcumin.44

Conclusion
A large number of epidemiologic, animal, and laboratory
studies indicate that abundant consumption of food of
plant origin reduces the risk of several types of cancer.
The chemopreventive effect is related to the high content
in these foods of phytochemicals with potent anticancer
and anti-inflammatory properties. These properties block
precancerous cells from developing into malignant cells
by interfering directly with tumour cells and by prevent-
ing generation of an inflammatory microenvironment
that would sustain the progression of the tumours. In Adapted from Béliveau and Gingras.10
many cases, these anticancer phytochemicals interfere

Table 5. Pharmacologic targets of diet-derived phytochemicals

TARGET EXAMPLES BEST FOOD SOURCES

Inhibition
Tumour invasion and metastasis Epigallocatechin gallate Green tea
Growth factor receptor–mediated signal transduction Delphinidin, ellagic acid Blueberries, raspberries, nuts
Inflammatory enzymes (eg, cyclooxygenase-2) Curcumin, resveratrol Turmeric, grapes
Transcription factor activity (eg, nuclear factor-κB, Curcumin, resveratrol Turmeric, grapes
activator protein-1)
Multidrug resistance Diallyl disulfide Garlic
Angiogenesis Epigallocatechin gallate Green tea
Estrogenic actions Genistein Soy
Metabolic activation of carcinogens via phase I enzymes Indole-3-carbinol Cabbage
Activation
Tumour cell apoptosis Phenethyl isothiocyanate Cabbage, watercress
Immune system function Lentinan Shiitake mushrooms
Detoxification via phase II enzymes Sulforaphane Broccoli

Vol 53:  november • novembre 2007  Canadian Family Physician • Le Médecin de famille canadien  1909
Clinical Review  Role of nutrition in preventing cancer
with tumour promotion and progression by mechanisms
identical to those through which synthetic molecularly
targeted chemotherapeutic agents exert their activity
(Table 5).7,42,45
Unlike synthetic molecules, however, whose inherent
toxicity limits their use for prevention (eg, COX-2 inhibi-
tors), the anticancer molecules present naturally in food
are selected by evolution to be beneficial for health and,
therefore, do not have secondary harmful effects. Daily
intake of food rich in anticancer molecules could thus
be compared to a preventive, non-toxic version of che-
motherapy that is harmless to the physiology of normal
tissue and stops microtumours from attaining a stage
that would allow them to have pathologic consequences.
Based on these considerations, there is no doubt that all
patients, particularly those who have family history of
cancer, should be strongly encouraged to change their
dietary habits to include at least 5 to 10 servings daily
of plant-based food, especially food with the highest
content of anticancer phytochemicals (Figure 210). Such
a change, coupled with a reduction in consumption of
red meat (which is associated with an increased risk of
colorectal46 and some types of breast47 cancer), main-
tenance of physical activity and appropriate body mass,
and not smoking could substantially reduce the burden
of cancer in Canada. 
Acknowledgment
This work was supported by grants from the Fondation
Charles-Bruneau and the Cancer Research Society of
Canada Inc. Dr Béliveau holds the Chaire en prévention
et en traitement du cancer at the University of Quebec at
Montreal and the Chaire Claude-Bertrand en neurochirur-
gie at the University of Montreal.
Competing interests
None declared
Correspondence to: Dr Richard Béliveau, Laboratoire
de Médecine Moléculaire, Centre de Recherche de l’Hôpital
Ste-Justine, 3175 chemin Côte-Ste-Catherine, Montréal,
QC H3T 1C5; telephone 514 345-2366; fax 514 345-2359;
e-mail beliveau.richard@uqam.ca
References
1. Doll R, Peto R. The causes of cancer: quantitative estimates of avoidable
risks of cancer in the United States today. J Natl Cancer Inst 1981;66:1191-308.
2. American Institute for Cancer Research, World Cancer Research Fund. Food,
nutrition, and the prevention of cancer: a global perspective. Washington, DC:
American Institute for Cancer Research; 1997.
3. Willett WC. Diet and cancer. Oncologist 2002;5:393-404.
4. Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M, et
al. Environmental and heritable factors in the causation of cancer—analy-
ses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med
2000;343:78-85.
5. Gescher A, Pastorino U, Plummer SM, Manson MM. Suppression of tumour
development by substances derived from the diet—mechanisms and clinical
implications. Br J Clin Pharmacol 1998;45:1-12.
6. Thomson CA, LeWinn K, Newton TR, Alberts DS, Martinez ME. Nutrition
and diet in the development of gastrointestinal cancer. Curr Oncol Rep
2003;5:192-202.
1910  Canadian Family Physician • Le Médecin de famille canadien  Vol 53:  november • novembre 2007
EDITOR’S KEY POINTS
• Even healthy people can have microtumours in their
tissues. It appears that the growth of these small
tumours is tightly controlled by our natural defence
mechanisms, but these defences can be over-
whelmed.
• Case-control, epidemiologic, and laboratory studies
have shown that certain foods of plant origin have
chemoprotective properties related to their ability
to block the progression of latent microtumours into
mature tumours.
• Canada’s Food Guide recommends intake of 7 to
10 servings of fruit and vegetables daily for adults,
depending on age and sex. It might be prudent to
choose foods that have high levels of anticancer
phytochemicals.
POINTS DE RÉPÈRE DU RÉDACTEUR
• Même une personne en santé peut héberger des
microtumeurs dans ses tissus. On croit que la
croissance de ces petites tumeurs est étroitement
contrôlée par les mécanismes de défense naturels,
mais ces défenses peuvent être débordées.
• Des études épidémiologiques, de cas-témoins
et en laboratoire ont montré que certains ali-
ments d’origine végétale possèdent des propriétés
chimioprotectrices reliées à leur capacité de blo-
quer la transformation des microtumeurs latentes
en tumeurs matures.
• Le Guide alimentaire canadien recommande pour les
adultes un apport quotidien de 7 à 10 portions de
fruits et légumes, selon l’âge et le sexe. Il semblerait
judicieux de choisir les aliments possédant un niveau
élevé de phytochimiques anticancéreux.
7. Surh YJ. Cancer chemoprevention with dietary phytochemicals. Nature Rev
Cancer 2003;3:768-80.
8. Dorai T, Aggarwal BB. Role of chemopreventive agents in cancer therapy.
Cancer Lett 2004;215:129-40.
9. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000;100:57-70.
10. Béliveau R, Gingras D. Foods that fight cancer: preventing cancer through diet.
Toronto, ON: McClelland & Stewart Ltd; 2006.
11. Black WC, Welch HG. Advances in diagnostic imaging and overesti-
mations of disease prevalence and the benefits of therapy. N Engl J Med
1993;328:1237-43.
12. Folkman J, Kalluri R. Cancer without disease [abstract]. Nature 2004;427:787.
13. Ames BN, Gold LS, Willett WC. The causes and prevention of cancer. Proc
Natl Acad Sci USA 1995;92:5258-65.
14. Ioannides C, Lewis DF. Cytochromes P450 in the bioactivation of chemicals.
Curr Top Med Chem 2004;4(16):1767-88.
15. Conney AH. Enzyme induction and dietary chemicals as approaches to can-
cer chemoprevention: the seventh DeWitt S. Goodman lecture. Cancer Res
2003;63:7005-31.
16. Talalay P. Chemoprotection against cancer by induction of phase 2 enzymes.
Biofactors 2000;12:5-11.
17. Hecht SS. Chemoprevention of cancer by isothiocyanates, modifiers of car-
cinogen metabolism. J Nutr 1999;129:768S-74S.
18. Talalay P, Fahey JW. Phytochemicals from cruciferous plants protect against
cancer by modulating carcinogen metabolism. J Nutr 2001;131:3027S-33S.
19. Guyonnet D, Belloir C, Suschetet M, Siess MH, Le Bon AM. Mechanisms of
protection against aflatoxin B(1) genotoxicity in rats treated by organosulfur
compounds from garlic. Carcinogenesis 2002;23:1335-41.
20. Hahn-Obercyger M, Stark AH, Madar Z. Grapefruit and oroblanco enhance
hepatic detoxification enzymes in rats: possible role in protection against
chemical carcinogenesis. J Agric Food Chem 2005;53:1828-32.
 Role of nutrition in preventing cancer  Clinical Review
21. Thornalley PJ. Isothiocyanates: mechanism of cancer chemopreventive
action. Anticancer Drugs 2002;13:331-8.
22. Karunagaran D, Rashmi R, Kumar TR. Induction of apoptosis by cur-
cumin and its implications for cancer therapy. Curr Cancer Drug Targets
2005;5:117-29.
23. Jang M, Cai L, Udeani GO, Slowing KV, Thomas CF, Beecher CW, et al.
Cancer chemopreventive activity of resveratrol, a natural product derived
from grapes. Science 1997;275:218-20.
24. Jeon KI, Rih JK, Kim HJ, Lee YJ, Cho CH, Goldberg ID, et al. Pretreatment of
indole-3-carbinol augments TRAIL-induced apoptosis in a prostate cancer
cell line, LNCaP. FEBS Lett 2003;544:246-51.
25. Jung EM, Park JW, Choi KS, Park JW, Lee HI, Lee KS, et al. Curcumin sen-
sitizes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-
mediated apoptosis through CHOP-independent DR5 upregulation.
Carcinogenesis 2006;27:2008-17.
26. Folkman J. Angiogenesis. Annu Rev Med 2006;57:1-18.
27. Tosetti F, Ferrari N, De Flora S, Albini A. “Angioprevention”: angiogenesis
is a common and key target for cancer chemopreventive agents. FASEB J
2002;16(1):2-14.
28. Béliveau R, Gingras D. Green tea: prevention and treatment of cancer by
nutraceuticals. Lancet 2004;364:1021-2.
29. Lamy S, Gingras D, Béliveau R. Green tea catechins inhibit vascu-
lar endothelial growth factor receptor phosphorylation. Cancer Res
2002;62:381-5.
30. Gupta S, Hastak K, Ahmad N, Lewin JS, Mukhtar H. Inhibition of prostate
carcinogenesis in TRAMP mice by oral infusion of green tea polyphenols.
Proc Natl Acad Sci USA 2001;98:10350-5.
31. Shanafelt TD, Lee YK, Call TG, Nowakowski GS, Dingli D, Zent CS, et al.
Clinical effects of oral green tea extracts in four patients with low grade B-
cell malignancies. Leuk Res 2006;30:707-12.
32. Labrecque L, Lamy S, Chapus A, Mihoubi S, Durocher Y, Cass B, et al.
Combined inhibition of PDGF and VEGF receptors by ellagic acid, a dietary-
derived phenolic compound. Carcinogenesis 2005;26:821-6.
33. Lamy S, Blanchette M, Michaud-Levesque J, Lafleur R, Durocher Y,
Moghrabi A, et al. Delphinidin, a dietary anthocyanidin, inhibits vascu-
lar endothelial growth factor receptor-2 phosphorylation. Carcinogenesis
2006;27:989-96.
✶✶✶
Vol 53:  november • novembre 2007  Canadian Family Physician • Le Médecin de famille canadien  1911
34. Bergers G, Song S, Meyer-Morse N, Bergsland E, Hanahan D. Benefits of
targeting both pericytes and endothelial cells in the tumour vasculature with
kinase inhibitors. J Clin Invest 2003;111:1287-95.
35. Coussens LM, Werb Z. Inflammation and cancer. Nature 2002;420:860-7.
36. Balkwill F, Charles KA, Mantovani A. Smoldering and polarized inflam-
mation in the initiation and promotion of malignant disease. Cancer Cell
2005;7:211-7.
37. Steinbach G, Lynch PM, Phillips RK, Wallace MH, Hawk E, Gordon GB, et al.
The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenoma-
tous polyposis. N Engl J Med 2000;342:1946-52.
38. Bertagnolli MM, Eagle CJ, Zauber AG, Redston N, Soloman SD, Kim K, et al.
Celecoxib for the prevention of sporadic colorectal adenomas. N Engl J Med
2006;355:873-84.
39. Giugliano D, Ceriello A, Esposito K. The effects of diet on inflammation:
emphasis on the metabolic syndrome. J Am Coll Cardiol 2006;48:677-85.
40. Calder PC. Dietary modification of inflammation with lipids. Proc Nutr Soc
2002;61:345-58.
41. Larsson SC, Kumlin M, Ingelman-Sundberg M, Wolk A. Dietary long-chain n-
3 fatty acids for the prevention of cancer: a review of potential mechanisms.
Am J Clin Nutr 2004;79:935-45.
42. Surh YJ, Chun KS, Cha HH, Han SS, Keum YS, Park KK, et al. Molecular
mechanisms underlying chemopreventive activities of anti-inflammatory phy-
tochemicals: down-regulation of COX-2 and iNOS through suppression of NF-
kappa B activation. Mutat Res 2001;480-1:243-68.
43. Aggarwal BB, Shishodia S. Suppression of the nuclear factor-kappaB activa-
tion pathway by spice-derived phytochemicals: reasoning for seasoning. Ann
NY Acad Sci 2004;1030:434-41.
44. Sharma RA, Euden SA, Platton SL, Cooke DN, Shafayat A, Hewitt HR, et al.
Phase I clinical trial of oral curcumin: biomarkers of systemic activity and
compliance. Clin Cancer Res 2004;10:6847-54.
45. D’Incalci M, Steward WP, Gescher AJ. Use of cancer chemopreventive phy-
tochemicals as antineoplastic agents. Lancet Oncol 2005;6:899-904.
46. Chao A, Thun MJ, Connell CJ, McCullough ML, Jacobs EJ, Flanders WD, et al.
Meat consumption and risk of colorectal cancer. JAMA 2005;293:172-82.
47. Cho E, Chen WY, Hunter DJ, Stampfer MJ, Colditz GA, Hankinson SE, et al.
Red meat intake and risk of breast cancer among premenopausal women.
Arch Intern Med 2006;166:253-9.